Glossary

CONSORT Glossary

Adjusted analysis - Usually refers to attempts to control (adjust) for baseline imbalances in important patient characteristics. Sometimes used to refer to adjustments of P value to take account of multiple testing. See also Multiple Comparisons below.

Adverse event - Pending definition

Allocation concealment - A technique used to prevent selection bias by concealing the allocation sequence from those assigning participants to intervention groups, until the moment of assignment. Allocation concealment prevents researchers from (unconsciously or otherwise) influencing which participants are assigned to a given intervention group.

Allocation ratio - The ratio of intended numbers of participants in each of the comparison groups. For two group trials, the allocation ratio is usually 1:1, but unequal allocation (such as 1:2) is sometimes used.

Ascertainment bias - Systematic distortion of the results of a randomized trial as a result of knowledge of the group assignment by the person assessing outcome, whether an investigator or the participant themselves.

B

Baseline characteristics - Values of demographic, clinical and other variables collected for each participant at the beginning of the trial, but before the intervention is administered. See also Prognostic variable below.

Bias - Systematic distortion of the estimated intervention effect away from the "truth", caused by inadequacies in the design, conduct, or analysis of a trial.

Blinding (masking) - The practice of keeping the trial participants, care providers, those collecting data, and sometimes even those analyzing data unaware of which intervention is being administered to which participant. Blinding is intended to prevent bias on the part of study personnel. The most common application is "double-blinding", in which participants, caregivers and those assessing outcome are blinded to intervention assignment. The term "masking" may be used instead of blinding.

Block randomisation - See Permuted block design below.

C

Clinical trial - An experiment to compare the effects of two or more healthcare interventions.

Clinical trial is an umbrella term for a variety of designs of healthcare trials, including uncontrolled trials, controlled trials, and randomised controlled trials.

Comparison groups - The groups being compared in the randomized trial. Also referred to as "study groups", "treatment groups", "the arms" of a trial, or by individual terms such as treatment and control groups.

Confidence intervals - A measure of the precision of an estimated value. The interval represents the range of values, consistent with the data, that is believed to encompass the "true" value with high probability (usually 95%). The confidence interval is expressed in the same units as the estimate. Wider intervals indicate lower precision; narrow intervals, greater precision.

Confounding - A situation in which the intervention effect is biased because of some difference between the comparison groups apart from the planned interventions, such as baseline characteristics, prognostic factors, or concomitant interventions. For a factor to be a confounder, it must differ between the comparison groups and predict the outcome of interest. See also Adjusted analysis above.

Controlled clinical trial - A clinical trial that has a control group. Such trials are not necessarily randomised. Controlled clinical trial (CCT) is an indexing term used in MEDLINE.

D

Deterministic method of allocation - A method of allocating participants to interventions that uses a pre-determined rule without a random element (e.g., alternate assignment, based on day of week, hospital number, or date of birth). Because group assignments can be predicted in advance of assignment in deterministic methods, participant allocation may be manipulated, causing selection bias. See also Selection bias below; Allocation concealment above .

E

Effect size - See Treatment effect below.

Eligibility criteria - The clinical and demographic characteristics that define those participants eligible to be enrolled in the trial.

Endpoint - See Outcome below.

Enrollment - The act of admitting a participant into a trial. Participants should be enrolled only after study personnel have confirmed that all the eligibility criteria have been met. Formal enrollment must occur before randomized assignment.

External validity - The extent to which the results of a trial provide a correct basis for generalizations to other circumstances. Also called "generalisability or "applicability".

F

Follow-up - A process of periodic contact with participants enrolled in the randomized trial for the purpose of administering the assigned intervention(s), modifying the course of intervention(s), observing the effects of the intervention(s), or for data collection. See also Loss to follow-up below.

G

Generation of allocation sequence - The procedure used to obtain the (random) sequence for making intervention assignments, such as use of a table of random numbers or a computerized random-number generator. Options such as simple randomization, blocked randomization, and stratified randomization are part of the generation of the allocation sequence.

H

Hypothesis - In a trial, a statement relating to the possible different effect of the interventions on an outcome. The null hypothesis of no such effect is amenable to explicit statistical evaluation by a hypothesis test, which generates a P value.

I

Imprecision - A quantification of the uncertainty in an estimate such as an effect size. Usually expressed as the 95% confidence interval around the estimate. Also refers more generally to other sources of uncertainty, such as measurement error.

Intention-to-treat analysis - A strategy for analyzing data in which all participants are included in the group to which they were assigned, whether or not they completed the intervention given to the group. Intention-to-treat analysis prevents bias caused by the loss of participants, which may disrupt the baseline equivalence established by random assignment and which may reflect non-adherence to the protocol.

Interaction - The situation in which the effect of one explanatory variable on the outcome is affected by the value of a second explanatory variable. In a trial, a test of interaction examines whether the treatment effect varies across subgroups of participants. See also Subgroup analysis below.

Interim analysis - Analysis comparing intervention groups at any time before the formal completion of the trial, usually before recruitment is complete. Often used with "stopping rules" so that a trial can be stopped if participants are being put at risk unnecessarily. Timing and frequency of interim analyses should be specified in the protocol.

Internal validity - The extent to which the design and conduct of the trial eliminate the possibility of bias.

Intervention - The treatment or other health care course of action under investigation. The effects of an intervention are quantified by the outcome measures.

L

Loss to follow-up - The circumstance that occurs when researchers lose contact with some participants and thus cannot complete planned data collection efforts. A common cause of missing data, especially in long-term studies. See also Follow-up above.

M

Minimization - An assignment strategy, similar in intention to stratification, that ensures excellent balance between intervention groups for specified prognostic factors. The next participant is assigned to whichever group would minimize the imbalance between groups on specified prognostic factors. Minimization is an acceptable alternative to random assignment.

Multiple comparisons - The performance of multiple analyses on the same data. Multiple statistical comparisons increase the probability of making a type I error, i.e. attributing a difference to an intervention when chance is the more likely explanation.

Multiplicity - The proliferation of possible comparisons in a trial. Common sources of multiplicity are multiple outcome measures, outcomes assessed at several time points after the intervention, and subgroup analyses. Also arises when there are multiple intervention groups.

O

Objectives - The general questions the trial was designed to answer. May be associated with one or more hypotheses that, when tested, will help answer the question. See also Hypothesis above.

Open trial - A randomized trial in which no one is blinded to group assignment.

Outcome (primary and secondary) - An outcome variable of interest in the trial (also called an end point). Differences between groups in the outcome variable(s) are believed to be the result of the differing interventions. The primary outcome is the outcome of greatest importance. Data on secondary outcomes are used to evaluate additional effects of the intervention.

P

Participant(s) - Study subjects who are selected to take part in a trial. They usually must meet certain eligibility criteria. See also Recruitment below, Enrollment above.

Performance bias - Systematic differences in the care provided to the participants in the comparison groups other than the intervention under investigation.

Permuted block design - An approach to generating an allocation sequence in which the number of assignments to intervention groups satisfies a specified allocation ratio (such as 1:1 or 2:1) after every "block" of specified size. For example, a block of size 12 would contain 6 A and 6 B with a ratio of 1:1 or 8 A and 4 B with a ratio of 2:1. Generating the allocation sequence involves randomly selecting from all the permutations of assignments that meet the specified ratio.

Planned analyses - Statistical analyses specified in the trial protocol (that is, planned in advance of data collection). Also called a priori analyses. In contrast to unplanned analyses (also called exploratory, data-derived or post hoc analyses), which are analyses suggested by the data. See also Subgroup analyses below.

Power - The probability that a trial will detect, as statistically significant, an intervention effect of a specified size. The prespecified trial size is often chosen to give the trial the desired power. See also Sample size below.

Precision - See Imprecision above.

Prognostic variable - A baseline variable that is prognostic in the absence of intervention Unrestricted, simple randomization can lead to chance baseline imbalance in prognostic variables, which can affect the results and weaken the trial's credibility. Stratification and minimization protect against such imbalances. See also Adjusted analysis above.

Protocol deviation - A failure to adhere to the pre-specified trial protocol, or a participant for whom this occurred. Examples are participants found to have been included in the trial by mistake (they were ineligible) and those for whom the intervention or other procedure differed from that outlined in the protocol.

R

Randomization - In a randomized trial, the process of assigning participants to groups such that each participant has a known and usually an equal chance of being assigned to a given group. Intended to ensure that the group assignment cannot be predicted.

Randomized controlled trial - An experiment in which two or more interventions, possibly including a control intervention or no intervention, are compared by being randomly allocated to participants. In most trials one intervention is assigned to each individual but sometimes assignment is to defined groups of individuals (for example, in a household) or interventions are assigned within individuals (for example, in different orders or to different parts of the body).

Recruitment - The process of getting participants into a randomized trial. See also Enrollment above.

Restricted randomization - Any procedure used with random assignment to achieve balance between study groups in size or baseline characteristics. Blocking is used to ensure that comparison groups will be of approximately the same size. With stratification, randomization with restriction is carried out separately within each of two or more subsets of participants (for example, defining disease severity or study centers) to ensure that the patient characteristics are closely balanced within each intervention group.

S

Sample size - The number of participants in the trial. The intended sample size is the number of participants planned to be included in the trial, usually determined using a statistical power calculation. The sample size should be adequate to provide a high probability of detecting as significant an effect size of a given magnitude if such an effect actually exists. The achieved sample size is the number of participants enrolled, treated or analyzed in the study.

Selection bias - Systematic error in creating intervention groups, such that they differ with respect to prognosis. That is, the groups differ in measured or unmeasured baseline characteristics because of the way participants were selected or assigned. Also used to mean that the participants are not representative of the population of all possible participants. See also Allocation concealment above, External validity above.

Side effect - An unintended, unexpected or undesirable result of an intervention. See also Adverse event above.

Simple randomization - Randomization without restriction. In a two-group trial, it is analogous to the toss of a coin. See also Restricted randomization above.

Stopping rule - In some trials, a statistical criterion that, when met by the accumulating data, indicates that the trial can or should be stopped early to avoid putting participants at risk unnecessarily or because the intervention effect is so great that further data collection is unnecessary. Usually defined in the trial protocol and implemented during a planned interim analysis. See also Interim analysis above.

Stratified randomization - Definition to follow

Subgroup analysis - An analysis in which the intervention effect is evaluated in a defined subset of the participants in the trial, or in complementary subsets, such as by sex or in age categories. Sample sizes in subgroup analyses are often small and subgroup analyses therefore usually lack statistical power. They are also subject to the multiple comparisons problem. See also Multiple comparisons above.

T

Treatment effect - A measure of the difference in outcome between intervention groups. Commonly expressed as a risk ratio (relative risk), odds ratio or risk difference for binary outcomes and as difference in means for continuous outcomes. Often referred to as the "effect size".